Methane limit LPS-induced NF-κB/MAPKs signal in macrophages and suppress immune response in mice by enhancing PI3K/AKT/GSK-3β-mediated IL-10 expression

Abstract

Inflammatory diseases such as sepsis and autoimmune colitis, characterized by an overwhelming activation of the immune system and the counteracting anti-inflammatory response, remain a major health problem in worldwide. Emerging evidence suggests that methane have a protective effect on many animal models, like ischaemia reperfusion injury and diabetes-associated diseases. Whether methane could modulating inflammatory diseases remains largely unknown. Here we show that methane-rich saline (MS) ip treatment (16 ml/kg) alleviated endotoxin shock, bacteria-induced sepsis and dextran-sulfate-sodium-induced colitis in mice via decreased production of TNF-α and IL-6. In MS-treated macrophages, LPS-induced activation of NF-κb/MAPKs was attenuated. Interestingly, MS treatment significantly elevated the levels of IL-10 both in vitro and in vivo. Neutralization of IL-10 abrogated the therapeutic effect of MS. Moreover, anti-IL10 blockade partially restored the MS-mediated attenuation of NF-κb/MAPKs phosphorylation. We further found that MS resulted in markedly enhanced phosphorylation of GSK-3β and AKT, which both mediate the release of Il-10. Additionally, inhibition of PI3K attenuated MS-mediated p-GSK-3β and IL-10 production and reversed the suppressed activation of NF-κb/ MAPKs in response to LPS. Our results reveal a novel effect and mechanisms of methane and support the potential value of MS as a therapeutic approach in innate inflammatory diseases.

Retracted: Knockdown of long noncoding RNA urothelial carcinoma–associated 1 inhibits cell viability, migration, and invasion by regulating microRNA‐182 in gastric carcinoma

“…37 It is clear that the PI3K/AKT/ GSK3β signal pathway plays an important role in regulating GC cells' apoptosis process. 37 It is clear that the PI3K/AKT/ GSK3β signal pathway plays an important role in regulating GC cells' apoptosis process.…”

Exposure to TNF-α combined with TGF-β induces carcinogenesis in vitro via NF-κB/Twist axis

“…Chronic inflammation-induced carcinogenesis and metastasis is a major challenge to cancer therapy, and is a key factor contributing to mortality in many malignancies (11)(12)(13)(14)(15)(16)(17). understanding the mechanisms regulating the metastasis and carcinogenesis induced by pro-inflammatory cytokines may lead to novel therapeutic interventions (17).…”

“…NF-κB is a classic transcription factor activated by inflammatory stimuli, such as LPS (11), TNF-α (12) and IL-10 (13). Activated NF-κB induces extensive gene expression in immune response (TNF-α), angiogenesis (VEGF), invasion (MMP-9) and EMT (Twist) (14)(15)(16)(17).…”

Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism

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